The stem cells of teratocarcinoma tumors, embryonal carcinoma cells, are derived from germ cells and primitive ectoderm cells of the early embryo. They are capable of responding to "cues" present in a developing embryo and will develop into benign, entirely normal cells when injected into early embryonic hosts. We have been studying the tumors formed when embryonal carcinoma cells are injected into adult hosts. They are distributed throughout the body in very unusual and unique patterns. The distribution of these "experimental metastases" depends on the route of injection. When cells are injected intraperitoneally (IP), tumors develop only in the ovaries of most mice. After left ventricle injection of the cells, tumors form in high frequencies in both sexes in the gonads, adrenals, eyes, and under the whiskers. Recent studies performed to determine the basis of this specificity suggest that this pattern of metastasis might be understood as the expression of properties characterizing the normal embryonic cell counterpart(s). Both germ cells and neuronal cells have extensive and highly specific migratory pathways that correspond in part to the sites of tumor production by embryonal carcinoma cells. Growth studies in vitro in defined media and direct implantation studies in mice indicate the cells are capable of growth in various sites and do not require organ-specific growth factors. In vitro adhesion assays and autoradiography studies indicate IP-injected cells preferentially attach to the ovarian germinal epithelium and then specifically invade the organ. 125IUDR-labeled cells injected in the heart are distributedroughly in proportion to the percent cardiac output. In vitro migration assays demonstrate that the cells are motile under some conditions and suggest that localized factors may promote the migration of cells trapped in the capillaries into the target organs. Putative factors and migration responses may be characterized using these cells in in vitro assays. Agents that block the specific metastases of these cells may then be more knowledgeably explored. (A)